Trial Outcomes & Findings for An Asian Study to Assess the Properties and Profile of Ticagrelor in Patients With Stable Coronary Artery Disease (NCT NCT01118325)
NCT ID: NCT01118325
Last Updated: 2014-07-08
Results Overview
Final extent IPA from pre-dose baseline was calculated using the following formula for Adenosine Diphosphate (ADP)-induced platelet aggregation: Percentage Inhibition = 100% x (PAs - PA) / (PAs) Platelet Aggregation (PA) was the mean response at the given post dose time point and PAs was the mean response at pre dose baseline. Percentage inhibition was restricted to the closed interval \[0,100\]; any data falling outside this range was truncated to the appropriate limit.
COMPLETED
PHASE2
146 participants
Week 4
2014-07-08
Participant Flow
In total, 146 patients were enrolled at 15 sites from 2 countries (Japan and Philippines). The study period was from April 2010 to March 2011. In total, 139 subjects were randomised and received the investigational product. Most subjects completed the study but 2 Japanese patients discontinued due to an AE during the 4 weeks treatment period.
Participant milestones
| Measure |
AZD6140 45 mg bd
AZD6140 45 mg twice daily
|
AZD6140 90 mg bd
AZD6140 90 mg twice daily
|
Clopidogrel 75 mg od
Clopidogrel 75 mg once daily
|
|---|---|---|---|
|
Overall Study
STARTED
|
50
|
43
|
46
|
|
Overall Study
COMPLETED
|
49
|
43
|
45
|
|
Overall Study
NOT COMPLETED
|
1
|
0
|
1
|
Reasons for withdrawal
| Measure |
AZD6140 45 mg bd
AZD6140 45 mg twice daily
|
AZD6140 90 mg bd
AZD6140 90 mg twice daily
|
Clopidogrel 75 mg od
Clopidogrel 75 mg once daily
|
|---|---|---|---|
|
Overall Study
Adverse Event
|
1
|
0
|
1
|
Baseline Characteristics
An Asian Study to Assess the Properties and Profile of Ticagrelor in Patients With Stable Coronary Artery Disease
Baseline characteristics by cohort
| Measure |
AZD6140 45 mg bd
n=50 Participants
AZD6140 45 mg twice daily
|
AZD6140 90 mg bd
n=43 Participants
AZD6140 90 mg twice daily
|
Clopidogrel 75 mg od
n=46 Participants
Clopidogrel 75 mg once daily
|
Total
n=139 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
63 Years
STANDARD_DEVIATION 11 • n=93 Participants
|
64 Years
STANDARD_DEVIATION 9 • n=4 Participants
|
64 Years
STANDARD_DEVIATION 10 • n=27 Participants
|
63 Years
STANDARD_DEVIATION 10 • n=483 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=93 Participants
|
3 Participants
n=4 Participants
|
8 Participants
n=27 Participants
|
15 Participants
n=483 Participants
|
|
Sex: Female, Male
Male
|
46 Participants
n=93 Participants
|
40 Participants
n=4 Participants
|
38 Participants
n=27 Participants
|
124 Participants
n=483 Participants
|
|
Race/Ethnicity, Customized
Japanese
|
42 Participants
n=93 Participants
|
35 Participants
n=4 Participants
|
40 Participants
n=27 Participants
|
117 Participants
n=483 Participants
|
|
Race/Ethnicity, Customized
Non-Japanese
|
8 Participants
n=93 Participants
|
8 Participants
n=4 Participants
|
6 Participants
n=27 Participants
|
22 Participants
n=483 Participants
|
PRIMARY outcome
Timeframe: Week 4Population: Only Japanese participants who had IPA data at Week 4 were considered in this analysis. Arm AZD6140 90 mg bd includes one non-Japanese participant resident in Japan
Final extent IPA from pre-dose baseline was calculated using the following formula for Adenosine Diphosphate (ADP)-induced platelet aggregation: Percentage Inhibition = 100% x (PAs - PA) / (PAs) Platelet Aggregation (PA) was the mean response at the given post dose time point and PAs was the mean response at pre dose baseline. Percentage inhibition was restricted to the closed interval \[0,100\]; any data falling outside this range was truncated to the appropriate limit.
Outcome measures
| Measure |
AZD6140 45 mg bd
n=41 Participants
AZD6140 45 mg twice daily in Japanese patients
|
AZD6140 90 mg bd
n=36 Participants
AZD6140 90 mg twice daily in Japanese patients
|
Clopidogrel 75 mg od
n=39 Participants
Clopidogrel 75 mg once daily
|
AZD6140 90 mg bd in Non-Japanese Patients
AZD6140 90 mg twice daily in non-Japanese patients
|
|---|---|---|---|---|
|
Inhibition of Platelet Aggregation(IPA) Final Extent at 2 Hours Post Dose on Week 4 in Japanese Patients
|
64.5 percentage inhibition
Standard Deviation 14.8
|
73.0 percentage inhibition
Standard Deviation 14.2
|
38.9 percentage inhibition
Standard Deviation 20.7
|
—
|
PRIMARY outcome
Timeframe: Week 4Population: Only Japanese participants who had IPA data at Week 4 were considered in this analysis. Arm AZD6140 90 mg bd includes one non-Japanese participant resident in Japan
Final extent IPA from pre-dose baseline was calculated using the following formula for ADP-induced platelet aggregation: Percentage Inhibition = 100% x (PAs - PA) / (PAs) PA was the mean response at the given post dose time point and PAs was the mean response at pre dose baseline. Percentage inhibition was restricted to the closed interval \[0,100\]; any data falling outside this range was truncated to the appropriate limit.
Outcome measures
| Measure |
AZD6140 45 mg bd
n=41 Participants
AZD6140 45 mg twice daily in Japanese patients
|
AZD6140 90 mg bd
n=36 Participants
AZD6140 90 mg twice daily in Japanese patients
|
Clopidogrel 75 mg od
n=39 Participants
Clopidogrel 75 mg once daily
|
AZD6140 90 mg bd in Non-Japanese Patients
AZD6140 90 mg twice daily in non-Japanese patients
|
|---|---|---|---|---|
|
IPA Final Extent at 4 Hours Post Dose on Week 4 in Japanese Patients
|
67.3 percentage inhibition
Standard Deviation 15.6
|
73.2 percentage inhibition
Standard Deviation 15.1
|
43.7 percentage inhibition
Standard Deviation 20.6
|
—
|
PRIMARY outcome
Timeframe: Week 4Population: Only Japanese participants who had IPA data at Week 4 were considered in this analysis. Arm AZD6140 90 mg bd includes one non-Japanese participant resident in Japan
Final extent IPA from pre-dose baseline was calculated using the following formula for ADP-induced platelet aggregation: Percentage Inhibition = 100% x (PAs - PA) / (PAs) PA was the mean response at the given post dose time point and PAs was the mean response at pre dose baseline. Percentage inhibition was restricted to the closed interval \[0,100\]; any data falling outside this range was truncated to the appropriate limit.
Outcome measures
| Measure |
AZD6140 45 mg bd
n=41 Participants
AZD6140 45 mg twice daily in Japanese patients
|
AZD6140 90 mg bd
n=36 Participants
AZD6140 90 mg twice daily in Japanese patients
|
Clopidogrel 75 mg od
n=39 Participants
Clopidogrel 75 mg once daily
|
AZD6140 90 mg bd in Non-Japanese Patients
AZD6140 90 mg twice daily in non-Japanese patients
|
|---|---|---|---|---|
|
IPA Final Extent at 8 Hours Post Dose on Week 4 in Japanese Patients
|
62.7 percentage inhibition
Standard Deviation 17.7
|
68.6 percentage inhibition
Standard Deviation 16.0
|
42.5 percentage inhibition
Standard Deviation 20.2
|
—
|
PRIMARY outcome
Timeframe: Week 4Population: Only Japanese participants who had IPA data at Week 4 were considered in this analysis. Arm AZD6140 90 mg bd includes one non-Japanese participant resident in Japan
Final extent IPA from pre-dose baseline was calculated using the following formula for ADP-induced platelet aggregation: Percentage Inhibition = 100% x (PAs - PA) / (PAs) PA was the mean response at the given post dose time point and PAs was the mean response at pre dose baseline. Percentage inhibition was restricted to the closed interval \[0,100\]; any data falling outside this range was truncated to the appropriate limit.
Outcome measures
| Measure |
AZD6140 45 mg bd
n=41 Participants
AZD6140 45 mg twice daily in Japanese patients
|
AZD6140 90 mg bd
n=36 Participants
AZD6140 90 mg twice daily in Japanese patients
|
Clopidogrel 75 mg od
n=39 Participants
Clopidogrel 75 mg once daily
|
AZD6140 90 mg bd in Non-Japanese Patients
AZD6140 90 mg twice daily in non-Japanese patients
|
|---|---|---|---|---|
|
IPA Final Extent at 12 Hours Post Dose on Week 4 in Japanese Patients
|
56.9 percentage inhibition
Standard Deviation 20.9
|
66.8 percentage inhibition
Standard Deviation 20.1
|
41.8 percentage inhibition
Standard Deviation 21.7
|
—
|
PRIMARY outcome
Timeframe: Week 4Population: Only Japanese participants who had IPA data at Week 4 were considered in this analysis. Arm AZD6140 90 mg bd includes one non-Japanese participant resident in Japan
Final extent IPA from pre-dose baseline was calculated using the following formula for ADP-induced platelet aggregation: Percentage Inhibition = 100% x (PAs - PA) / (PAs) PA was the mean response at the given post dose time point and PAs was the mean response at pre dose baseline. Percentage inhibition was restricted to the closed interval \[0,100\]; any data falling outside this range was truncated to the appropriate limit.
Outcome measures
| Measure |
AZD6140 45 mg bd
n=41 Participants
AZD6140 45 mg twice daily in Japanese patients
|
AZD6140 90 mg bd
n=36 Participants
AZD6140 90 mg twice daily in Japanese patients
|
Clopidogrel 75 mg od
n=39 Participants
Clopidogrel 75 mg once daily
|
AZD6140 90 mg bd in Non-Japanese Patients
AZD6140 90 mg twice daily in non-Japanese patients
|
|---|---|---|---|---|
|
IPA Final Extent at 24 Hours Post Dose on Week 4 in Japanese Patients
|
46.2 percentage inhibition
Standard Deviation 23.3
|
59.1 percentage inhibition
Standard Deviation 20.3
|
38.0 percentage inhibition
Standard Deviation 20.5
|
—
|
SECONDARY outcome
Timeframe: Week 4Population: Only Japanese participants who had IPA data at Week 4 were considered in this analysis
Maximum plasma AZD6140 concentration
Outcome measures
| Measure |
AZD6140 45 mg bd
n=38 Participants
AZD6140 45 mg twice daily in Japanese patients
|
AZD6140 90 mg bd
n=8 Participants
AZD6140 90 mg twice daily in Japanese patients
|
Clopidogrel 75 mg od
n=33 Participants
Clopidogrel 75 mg once daily
|
AZD6140 90 mg bd in Non-Japanese Patients
n=7 Participants
AZD6140 90 mg twice daily in non-Japanese patients
|
|---|---|---|---|---|
|
AZD6140 (Cmax) at Week 4
|
422 ng/mL
Standard Deviation 230
|
341 ng/mL
Standard Deviation 370
|
931 ng/mL
Standard Deviation 442
|
1380 ng/mL
Standard Deviation 343
|
SECONDARY outcome
Timeframe: Week 4Population: In total 7 Japanese patients (4 patients in 45 mg and 3 patients in 90 mg) were excluded from the PK analysis set since PK samples of these patients were discarded due to a database set-up issue at the central laboratory.
Area under the plasma concentration curve of AZD6140 from time zero to dosing interval
Outcome measures
| Measure |
AZD6140 45 mg bd
n=38 Participants
AZD6140 45 mg twice daily in Japanese patients
|
AZD6140 90 mg bd
n=8 Participants
AZD6140 90 mg twice daily in Japanese patients
|
Clopidogrel 75 mg od
n=33 Participants
Clopidogrel 75 mg once daily
|
AZD6140 90 mg bd in Non-Japanese Patients
n=7 Participants
AZD6140 90 mg twice daily in non-Japanese patients
|
|---|---|---|---|---|
|
AZD6140 (AUC0-tau) at Week 4
|
3050 ng.h/mL
Standard Deviation 1940
|
2930 ng.h/mL
Standard Deviation 3740
|
6080 ng.h/mL
Standard Deviation 2600
|
10900 ng.h/mL
Standard Deviation 2790
|
SECONDARY outcome
Timeframe: Week 4Population: In total 7 Japanese patients (4 patients in 45 mg and 3 patients in 90 mg) were excluded from the PK analysis set since PK samples of these patients were discarded due to a database set-up issue at the central laboratory.
Time to reach peak or maximum concentration of AZD6140 following AZD6140 administration
Outcome measures
| Measure |
AZD6140 45 mg bd
n=38 Participants
AZD6140 45 mg twice daily in Japanese patients
|
AZD6140 90 mg bd
n=8 Participants
AZD6140 90 mg twice daily in Japanese patients
|
Clopidogrel 75 mg od
n=33 Participants
Clopidogrel 75 mg once daily
|
AZD6140 90 mg bd in Non-Japanese Patients
n=7 Participants
AZD6140 90 mg twice daily in non-Japanese patients
|
|---|---|---|---|---|
|
AZD6140 (Tmax) at Week 4
|
2.0 hour
Interval 1.9 to 4.0
|
4.0 hour
Interval 2.0 to 4.0
|
2.0 hour
Interval 1.9 to 4.1
|
4.0 hour
Interval 2.0 to 4.1
|
SECONDARY outcome
Timeframe: Week 4Population: In total 7 Japanese patients (4 patients in 45 mg and 3 patients in 90 mg) were excluded from the PK analysis set since PK samples of these patients were discarded due to a database set-up issue at the central laboratory.
Maximum plasma concentration of AZD6140 drug metabolite AR-C124910XX
Outcome measures
| Measure |
AZD6140 45 mg bd
n=38 Participants
AZD6140 45 mg twice daily in Japanese patients
|
AZD6140 90 mg bd
n=8 Participants
AZD6140 90 mg twice daily in Japanese patients
|
Clopidogrel 75 mg od
n=33 Participants
Clopidogrel 75 mg once daily
|
AZD6140 90 mg bd in Non-Japanese Patients
n=7 Participants
AZD6140 90 mg twice daily in non-Japanese patients
|
|---|---|---|---|---|
|
AR-C124910XX (Cmax) at Week 4
|
135 ng/mL
Standard Deviation 53.3
|
101 ng/mL
Standard Deviation 72.4
|
326 ng/mL
Standard Deviation 139
|
381 ng/mL
Standard Deviation 192
|
SECONDARY outcome
Timeframe: Week 4Population: In total 7 Japanese patients (4 patients in 45 mg and 3 patients in 90 mg) were excluded from the PK analysis set since PK samples of these patients were discarded due to a database set-up issue at the central laboratory.
Area under the plasma concentration curve of AZD6140 drug metabolite AR-C124910XX from time zero to dosing interval
Outcome measures
| Measure |
AZD6140 45 mg bd
n=38 Participants
AZD6140 45 mg twice daily in Japanese patients
|
AZD6140 90 mg bd
n=8 Participants
AZD6140 90 mg twice daily in Japanese patients
|
Clopidogrel 75 mg od
n=33 Participants
Clopidogrel 75 mg once daily
|
AZD6140 90 mg bd in Non-Japanese Patients
n=7 Participants
AZD6140 90 mg twice daily in non-Japanese patients
|
|---|---|---|---|---|
|
AR-C124910XX (AUC0-tau) at Week 4
|
1180 ng.h/mL
Standard Deviation 490
|
954 ng.h/mL
Standard Deviation 741
|
2720 ng.h/mL
Standard Deviation 915
|
3380 ng.h/mL
Standard Deviation 1580
|
SECONDARY outcome
Timeframe: Week 4Population: In total 7 Japanese patients (4 patients in 45 mg and 3 patients in 90 mg) were excluded from the PK analysis set since PK samples of these patients were discarded due to a database set-up issue at the central laboratory.
Time to reach peak or maximum concentration of AZD6140 drug metabolite AR-C124910XX following AZD6140 administration
Outcome measures
| Measure |
AZD6140 45 mg bd
n=38 Participants
AZD6140 45 mg twice daily in Japanese patients
|
AZD6140 90 mg bd
n=8 Participants
AZD6140 90 mg twice daily in Japanese patients
|
Clopidogrel 75 mg od
n=33 Participants
Clopidogrel 75 mg once daily
|
AZD6140 90 mg bd in Non-Japanese Patients
n=7 Participants
AZD6140 90 mg twice daily in non-Japanese patients
|
|---|---|---|---|---|
|
AR-C124910XX (Tmax) at Week 4
|
4.0 hour
Interval 1.9 to 11.9
|
4.0 hour
Interval 2.0 to 8.0
|
2.1 hour
Interval 1.9 to 8.0
|
2.0 hour
Interval 2.0 to 4.0
|
Adverse Events
AZD6140 45 mg bd
AZD6140 90 mg bd
Clopidogrel 75 mg od
Serious adverse events
| Measure |
AZD6140 45 mg bd
n=50 participants at risk
AZD6140 45 mg twice daily
|
AZD6140 90 mg bd
n=43 participants at risk
AZD6140 90 mg twice daily
|
Clopidogrel 75 mg od
n=46 participants at risk
Clopidogrel 75 mg once daily
|
|---|---|---|---|
|
Gastrointestinal disorders
GASTROINTESTINAL HAEMORRHAGE
|
2.0%
1/50 • Number of events 1
|
0.00%
0/43
|
0.00%
0/46
|
|
Respiratory, thoracic and mediastinal disorders
PNEUMONIA
|
2.0%
1/50 • Number of events 1
|
0.00%
0/43
|
0.00%
0/46
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
LIP AND/OR ORAL CAVITYCANCER
|
0.00%
0/50
|
2.3%
1/43 • Number of events 1
|
0.00%
0/46
|
Other adverse events
| Measure |
AZD6140 45 mg bd
n=50 participants at risk
AZD6140 45 mg twice daily
|
AZD6140 90 mg bd
n=43 participants at risk
AZD6140 90 mg twice daily
|
Clopidogrel 75 mg od
n=46 participants at risk
Clopidogrel 75 mg once daily
|
|---|---|---|---|
|
Skin and subcutaneous tissue disorders
Haemorrhage subcutaneous
|
18.0%
9/50
|
20.9%
9/43
|
6.5%
3/46
|
|
Infections and infestations
Nasopharyngitis
|
2.0%
1/50
|
16.3%
7/43
|
6.5%
3/46
|
|
Gastrointestinal disorders
Abdominal discomfort
|
4.0%
2/50
|
4.7%
2/43
|
4.3%
2/46
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
2.0%
1/50
|
2.3%
1/43
|
4.3%
2/46
|
|
Nervous system disorders
Headache
|
4.0%
2/50
|
2.3%
1/43
|
0.00%
0/46
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/50
|
4.7%
2/43
|
0.00%
0/46
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
|
0.00%
0/50
|
4.7%
2/43
|
0.00%
0/46
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/50
|
4.7%
2/43
|
0.00%
0/46
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60